{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T19:24:59Z","timestamp":1789068299958,"version":"build-2803163510"},"reference-count":126,"publisher":"SAGE Publications","issue":"17-18","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Stem Cells and Development"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>The dental pulp not only serves as the tooth\u2019s nutritional core but also creates a finely tuned microenvironment that is enriched with blood vessels, nerves, extracellular matrix components, and signaling molecules, all of which guide the fate of resident dental pulp stem cells (DPSCs). Trauma and microbial invasion disrupt this niche, leading to pulpitis and necrosis. Although conventional root canal treatment preserves the tooth\u2019s structure by removing infected pulp, it can increase tooth brittleness and impede root development in immature permanent teeth. Harnessing DPSCs\u2019 multipotency for pulp regeneration promises to restore the natural pulp\u2013dentin complex in situ. Importantly, DPSCs encounter an inflammatory microenvironment composed of pathogen-associated molecular patterns, a spectrum of pro- and anti-inflammatory cytokines, diverse immune cell phenotypes, and altered matrix signals. While earlier work examined the isolated effects of mediators such as lipopolysaccharide, tumor necrosis factor-alpha, or macrophage-derived exosomes on odontogenic differentiation, this review focuses on how these mediators collectively interact in both synergistic and antagonistic ways within the inflammatory niche. We systematically delineate how these collective stimuli converge on wingless\/integrated\/beta-catenin, mitogen-activated protein kinase, nuclear factor kappa-B (NF-\u03baB), and bone morphogenetic protein\/Sma and Mad related protein pathways to modulate key odontogenic markers (runt-related transcription factor 2, dentin sialophosphoprotein, dentin matrix protein 1, alkaline phosphatase) and mineralization outcomes. By applying a microenvironment-centric lens, we reveal novel targets and strategies to recalibrate inflammation, steer DPSCs toward reparative odontogenesis, and ultimately enhance the efficacy of regenerative endodontic therapies.<\/jats:p>","DOI":"10.1177\/15473287251366979","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T19:22:39Z","timestamp":1757618559000},"page":"374-384","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effect of the Inflammatory Microenvironment on Odontogenic Differentiation of Dental Pulp Stem Cells"],"prefix":"10.1177","volume":"34","author":[{"given":"Shangzhou","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youkai","family":"Lin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingming","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6981-7081","authenticated-orcid":false,"given":"Xuelian","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oral Diseases &amp; National Center of Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; Department of Operative Dentistry and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.656588"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1394582"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/iej.12954"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00058"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-021-00389-2"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.11.015"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.857066"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168991"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/154405910208100806"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.240309797"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116990"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.12669\/pjms.38.5.5187"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4709572"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-025-10883-y"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2018.11.009"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2021.121223"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0506-5"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-013-1030-3"},{"key":"e_1_3_4_20_2","first-page":"129","article-title":"Role of dental pulp stem cells to promote angiogenesis in cell-based regenerative endodontics","volume":"26","author":"Tang MQ","year":"2023","unstructured":"Tang MQ, , Ye L, , Gao B. Role of dental pulp stem cells to promote angiogenesis in cell-based regenerative endodontics. Chin J Dent Res, 2023; 26:129\u2013142.","journal-title":"Chin J Dent Res"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0887-z"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0103-9"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.870324"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02985-y"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1272764"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-21705-5_8"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509340867"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-03145-6"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v042a04"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.12.012"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-021-10162-6"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01685"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.7b19782"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034520967353"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2004.07.013"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11596-9"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-023-00918-9"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx063"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.27231"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2017.11.018"},{"key":"e_1_3_4_41_2","first-page":"269","article-title":"MiR-146a-5p promotes dental stem cells osteo\/odontogenic differentiation through NF-Kappa B signaling pathway by targeting TRAF6","volume":"25","author":"Yu X","year":"2022","unstructured":"Yu X, , Lu JF, , Gao MQ, et al. MiR-146a-5p promotes dental stem cells osteo\/odontogenic differentiation through NF-Kappa B signaling pathway by targeting TRAF6. Chin J Dent Res, 2022; 25:269\u2013275.","journal-title":"Chin J Dent Res"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.3390\/polym12092125"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2020.103413"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.2174\/1574888X11666160815095733"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23041984"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2010.12.008"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.665886"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2023.02.002"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.2217\/rme.10.30"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep19286"},{"key":"e_1_3_4_51_2","first-page":"1819","article-title":"Loss of Wnt4 expression inhibits the odontogenic potential of dental pulp stem cells through JNK signaling in pulpitis","volume":"11","author":"Zhong T-Y","year":"2019","unstructured":"Zhong T-Y, , Zhang Z-C, , Gao Y-N, et al. Loss of Wnt4 expression inhibits the odontogenic potential of dental pulp stem cells through JNK signaling in pulpitis. Am J Transl Res, 2019; 11:1819\u20131826.","journal-title":"Am J Transl Res"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2019.0106"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2012.02.014"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0633-z"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031480"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdsr.2018.03.001"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/794143"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.812774"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.5.1698-1704.2002"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-51-12-1090"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.45976-0"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2010.11.020"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13720"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10938"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25084338"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2016.00040"},{"key":"e_1_3_4_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-022-00158-4"},{"key":"e_1_3_4_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24732"},{"key":"e_1_3_4_69_2","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2023.2218944"},{"key":"e_1_3_4_70_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2591.2012.02096.x"},{"key":"e_1_3_4_71_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1247-4"},{"key":"e_1_3_4_72_2","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13448"},{"key":"e_1_3_4_73_2","first-page":"823","article-title":"Time-dependent C5a and C5aR expression in dental pulp cells following stimulation with LTA and LPS","volume":"44","author":"Liu M","year":"2019","unstructured":"Liu M, , Mu H, , Peng W, et al. Time-dependent C5a and C5aR expression in dental pulp cells following stimulation with LTA and LPS. Int J Mol Med, 2019; 44:823\u2013834.","journal-title":"Int J Mol Med"},{"key":"e_1_3_4_74_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells12141851"},{"key":"e_1_3_4_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2014.07.004"},{"key":"e_1_3_4_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2019.154896"},{"key":"e_1_3_4_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101540"},{"key":"e_1_3_4_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11626-016-0070-9"},{"key":"e_1_3_4_79_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0113419"},{"key":"e_1_3_4_80_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10141"},{"key":"e_1_3_4_81_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03057-x"},{"key":"e_1_3_4_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.09.081"},{"key":"e_1_3_4_83_2","doi-asserted-by":"publisher","DOI":"10.1111\/dgd.12233"},{"key":"e_1_3_4_84_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.51362"},{"key":"e_1_3_4_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2019.08.002"},{"key":"e_1_3_4_86_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-023-03020-z"},{"key":"e_1_3_4_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2017.05.008"},{"key":"e_1_3_4_88_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02141-y"},{"key":"e_1_3_4_89_2","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.1312"},{"key":"e_1_3_4_90_2","doi-asserted-by":"publisher","DOI":"10.3390\/biom13010118"},{"key":"e_1_3_4_91_2","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.00161"},{"key":"e_1_3_4_92_2","doi-asserted-by":"publisher","DOI":"10.1089\/cell.2018.0031"},{"key":"e_1_3_4_93_2","article-title":"Decreasing NF-\u03baB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines","volume":"10","author":"Hozhabri NST","year":"2015","unstructured":"Hozhabri NST, , Benson MD, , Vu MD, et al. Decreasing NF-\u03baB expression enhances odontoblastic differentiation and collagen expression in dental pulp stem cells exposed to inflammatory cytokines. PLoS One, 2015; 10:e0113334.","journal-title":"PLoS One"},{"key":"e_1_3_4_94_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03277-0"},{"key":"e_1_3_4_95_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.020"},{"key":"e_1_3_4_96_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2361376"},{"key":"e_1_3_4_97_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15754"},{"key":"e_1_3_4_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jds.2022.06.027"},{"key":"e_1_3_4_99_2","doi-asserted-by":"publisher","DOI":"10.1111\/eos.12956"},{"key":"e_1_3_4_100_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-04863-y"},{"key":"e_1_3_4_101_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-022-04443-8"},{"key":"e_1_3_4_102_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2020.103501"},{"key":"e_1_3_4_103_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12020441"},{"key":"e_1_3_4_104_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2017.06.011"},{"key":"e_1_3_4_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2020.06.019"},{"key":"e_1_3_4_106_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29713"},{"key":"e_1_3_4_107_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-023-01910-6"},{"key":"e_1_3_4_108_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-023-03625-4"},{"key":"e_1_3_4_109_2","doi-asserted-by":"publisher","DOI":"10.22203\/eCM.v041a13"},{"key":"e_1_3_4_110_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/3060480"},{"key":"e_1_3_4_111_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10081999"},{"key":"e_1_3_4_112_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034516657817"},{"key":"e_1_3_4_113_2","doi-asserted-by":"publisher","DOI":"10.21037\/atm-22-6390"},{"key":"e_1_3_4_114_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108043"},{"key":"e_1_3_4_115_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2022.101944"},{"key":"e_1_3_4_116_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2007.01.002"},{"key":"e_1_3_4_117_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101212"},{"key":"e_1_3_4_118_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01471-y"},{"key":"e_1_3_4_119_2","doi-asserted-by":"publisher","DOI":"10.1111\/iej.14001"},{"key":"e_1_3_4_120_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02236-6"},{"key":"e_1_3_4_121_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13577-014-0106-y"},{"key":"e_1_3_4_122_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2016.08.008"},{"key":"e_1_3_4_123_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4682875"},{"key":"e_1_3_4_124_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179578"},{"key":"e_1_3_4_125_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-019-09088-6"},{"key":"e_1_3_4_126_2","doi-asserted-by":"publisher","DOI":"10.3349\/ymj.2017.58.5.1031"},{"key":"e_1_3_4_127_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joen.2016.09.005"}],"container-title":["Stem Cells and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/15473287251366979","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15473287251366979","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/15473287251366979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T07:13:30Z","timestamp":1777706010000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/15473287251366979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":126,"journal-issue":{"issue":"17-18","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1177\/15473287251366979"],"URL":"https:\/\/doi.org\/10.1177\/15473287251366979","relation":{},"ISSN":["1547-3287","1557-8534"],"issn-type":[{"value":"1547-3287","type":"print"},{"value":"1557-8534","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]}}}